Advanced Glycated End Products Alter Neutrophil Effect on Regulation of CD+ T Cell Differentiation Through Induction of Myeloperoxidase and Neutrophil Elastase Activities.

CD T cell subset imbalance plays an important role in the development of diabetic complications. Neutrophils have recently been known as the regulator of CD T cell differentiation. However, whether neutrophils affect CD T cell population in diabetes is still elusive. In this study, we investigated the effect of neutrophils stimulated with advanced glycated end products (AGEs), the marker of diabetes, on CD T cell differentiation and its underlying mechanism. Our data showed that the cultural medium of healthy adult neutrophils treated with AGEs increased expressions of both Th (IFN-γ) and Th (IL-17) phenotypes and the transcription factors of Th (Tbet) and Th (RORγt) in naive CDT cells and CDCDFoxP (Treg) T cells in vitro. Next, we found that AGEs induced the generations of myeloperoxidase (MPO) and neutrophil elastase (NE) in neutrophils; inhibition of MPO or NE attenuated the effect of AGE-stimulated neutrophils on CD T cell bias. Furthermore, receptor for AGEs (RAGE) inhibitor interrupted AGE-induced MPO and NE expressions, but MPO and NE inhibitions did not change AGE-increased RAGE gene expression. These results suggested that AGEs drive the effect of neutrophils on CD T cell differentiation into pro-inflammatory program through inducing MPO and NE productions in neutrophils, which is mediated by AGE-RAGE interaction.